Uncharacterized conserved protein, contains RING Zn-finger [General function prediction only];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198041681   59 SLVDSDFRMVLRKLSKKDVTTKLKAMQEFGTMC--TERDTEAvkgVLPYWPRIFCKISLDHDRRVREATQQAFEKLILKV 136
Cdd:COG5219    40 SGLDAEMIVIVKNLQKRDIVTKCRALQDLIQWNdpSQFDNEQ---FLNALAVLFPRLSIEVEMNPRLEGLQFDSRLYEIL 116

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 198041681  137 KKHLAPYLKSVMGYWLMAQCDTYPPAATAAKDAFEAAFPPSKQPEAIVFCKEEITTVLQDHLLKETPDTLSDPQTVPEEE 216
Cdd:COG5219   117 SKKIGKRLKKTILRGLLGLKDVDDTVSVEANIDTLLEIVEDKWPTIWKSFNLQIKNLVIDVLYHELLSSVEDRRKFSKEE 196

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 198041681  217 REAKFHRVVTCSLLALKRLLCFLPNNELDSlEEKFRSLLSQNKFWK 262
Cdd:COG5219   197 SEWLYGRVENSEYLVLRKLFAEFVDIGLET-DKKIEKQTLEDSFVR 241

RING-CH finger, H2 subclass (C4HC3-type), found in E3 ubiquitin-protein ligase listerin and similar proteins; Listerin, also known as RING finger protein 160 or zinc finger protein 294, is the mammalian homolog of yeast Ltn1. It is widely expressed in all tissues, but motor and sensory neurons and neuronal processes in the brainstem and spinal cord are primarily affected in the mutant. Listerin is required for embryonic development and plays an important role in neurodegeneration. It also functions as a critical E3 ligase involving quality control of nonstop proteins. It mediates ubiquitylation of aberrant proteins that become stalled on ribosomes during translation. Ltn1 works with several cofactors to form a large ribosomal subunit-associated quality control complex (RQC), which mediates the ubiquitylation and extraction of ribosome-stalled nascent polypeptide chains for proteasomal degradation. It appears to first associate with nascent chain-stalled 60S subunits together with two proteins of unknown function, Tae2 and Rqc1. Listerin contains a long stretch of HEAT (Huntingtin, Elongation factor 3, PR65/A subunit of protein phosphatase 2A, and TOR) or ARM (Armadillo) repeats in the N terminus and middle region, and a catalytic RING-CH finger, also known as vRING or RINGv, with an unusual arrangement of zinc-coordinating residues in the C-terminus . Its cysteines and histidines are arranged in the sequence as C4HC3-type, rather than the C3H2C3-type in canonical RING-H2 finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 198041681 1714 EDCMICFSVIHGFNYSLPKKACRTCKKKFHSACLYKWFTSSNKSTCPLCR 1763
Cdd:cd16491     1 EECPICYSVIHGSNHSLPKLKCKTCKNKFHSACLYKWFRSSNKSTCPLCR 50

Ring finger domain;

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 198041681  1715 DCMICFSvihgfNYSLPKKACRT-CKKKFHSACLYKWFTSSNksTCPLCR 1763
Cdd:pfam13639    2 ECPICLE-----EFEEGDKVVVLpCGHHFHRECLDKWLRSSN--TCPLCR 44

RING-CH finger, H2 subclass (C4HC3-type), found in E3 ubiquitin-protein ligase listerin and similar proteins; Listerin, also known as RING finger protein 160 or zinc finger protein 294, is the mammalian homolog of yeast Ltn1. It is widely expressed in all tissues, but motor and sensory neurons and neuronal processes in the brainstem and spinal cord are primarily affected in the mutant. Listerin is required for embryonic development and plays an important role in neurodegeneration. It also functions as a critical E3 ligase involving quality control of nonstop proteins. It mediates ubiquitylation of aberrant proteins that become stalled on ribosomes during translation. Ltn1 works with several cofactors to form a large ribosomal subunit-associated quality control complex (RQC), which mediates the ubiquitylation and extraction of ribosome-stalled nascent polypeptide chains for proteasomal degradation. It appears to first associate with nascent chain-stalled 60S subunits together with two proteins of unknown function, Tae2 and Rqc1. Listerin contains a long stretch of HEAT (Huntingtin, Elongation factor 3, PR65/A subunit of protein phosphatase 2A, and TOR) or ARM (Armadillo) repeats in the N terminus and middle region, and a catalytic RING-CH finger, also known as vRING or RINGv, with an unusual arrangement of zinc-coordinating residues in the C-terminus . Its cysteines and histidines are arranged in the sequence as C4HC3-type, rather than the C3H2C3-type in canonical RING-H2 finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 198041681 1714 EDCMICFSVIHGFNYSLPKKACRTCKKKFHSACLYKWFTSSNKSTCPLCR 1763
Cdd:cd16491     1 EECPICYSVIHGSNHSLPKLKCKTCKNKFHSACLYKWFRSSNKSTCPLCR 50

H2 subclass of RING (RING-H2) fingers and its variants; The RING finger is a specialized type of Zn-finger of 40 to 60 residues that binds two atoms of zinc. It is defined by the "cross-brace" motif that chelates zinc atoms by eight amino acid residues, typically Cys or His, arranged in a characteristic spacing. Canonical RING motifs have been categorized into two major subclasses, RING-HC (C3HC4-type) and RING-H2 (C3H2C3-type), according to their Cys/His content. There are also many variants of RING fingers: some have different Cys/His patterns while some lack a single Cys or His residue at typical Zn ligand positions (the fourth or eighth zinc ligand is prevalently exchanged for an Asp, which can indeed chelate Zn in a RING finger as well). This family corresponds to the H2 subclass of RING (RING-H2) finger proteins that are characterized by containing C3H2C3-type canonical RING-H2 fingers or noncanonical RING-H2 finger variants, including C4HC3- (RING-CH alias RINGv), C3H3C2-, C3H2C2D-, C3DHC3-, and C4HC2H-type modified RING-H2 fingers. The canonical RING-H2 finger has been defined as C-X2-C-X(9-39)-C-X(1-3)-H-X(2-3)-H-X2-C-X(4-48)-C-X2-C, X is any amino acid and the number of X residues varies in different fingers. It binds two Zn ions in a unique "cross-brace" arrangement, which distinguishes it from tandem zinc fingers and other similar motifs. RING-H2 finger can be found in a group of diverse proteins with a variety of cellular functions, including oncogenesis, development, viral replication, signal transduction, the cell cycle and apoptosis. Many of them are ubiquitin-protein ligases (E3s) that serves as a scaffold for binding to ubiquitin-conjugating enzymes (E2s, also referred to as ubiquitin carrier proteins or UBCs) in close proximity to substrate proteins, which enables efficient transfer of ubiquitin from E2 to the substrates.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 198041681 1716 CMICFSVIHGFNyslpKKACRTCKKKFHSACLYKWFTSSNKsTCPLCR 1763
Cdd:cd16448     1 CVICLEEFEEGD----VVRLLPCGHVFHLACILRWLESGNN-TCPLCR 43

RING-CH finger, H2 subclass (C4HC3-type), found in Fanconi anemia group L protein (FANCL) and similar proteins; FANCL, also known as fanconi anemia-associated polypeptide of 43 kDa (FAAP43) or PHF9, is a monomeric RING E3 ubiquitin-protein ligase that monoubiquitinates FANCD2 and FANCI. The monoubiquitinated FANCD2-FANCI heterodimer complex in turn recruits key proteins involved in homologous recombination and DNA repair. FANCL is also one of seven components in Fanconi anemia (FA) nuclear core complex, which provides the essential E3 ligase function for spatially defined FANCD2 ubiquitination and FA pathway activation. In the FA core complex, FANCL associates with FANCB and FAAP100 to constitute a catalytic subcomplex that functions as the monoubiquitination module. FANCL specifically interacts with the E2 ubiquitin-conjugating (UBC) enzyme Ube2T to make an E3-E2 pair, which is the catalytic center of the Fanconi Anemia (FA) pathway required for DNA interstrand crosslink repair. Moreover, FANCL has a noncanonical function to regulate the Wnt/beta-catenin signaling, a pathway involved in hematopoietic stem cell self-renewal. It functionally enhances beta-catenin activity by ubiquitinating beta-catenin, with atypical ubiquitin chains (K11 linked). FANCL contains an N-terminal E2-like fold (ELF) domain, a novel double-RWD (DRWD) domain with a clear hydrophobic core, and a C-terminal C4HC3-type RING-CH finger. The DRWD domain is required for substrate binding. The RING-CH finger, also known as vRING or RINGv, is predicted to facilitate E2 binding. It has an unusual arrangement of zinc-coordinating residues. Its cysteines and histidines are arranged in the sequence as C4HC3-type, rather than the C3H2C3-type in canonical RING-H2 finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 198041681 1715 DCMICFSviHGFNYSLPKKACR--TCKKKFHSACLYKWF---TSSNKS------TCPLC 1762
Cdd:cd16490     1 ECGICYA--YRLDGEVPDQVCDnaRCGQPFHQSCLYEWLrslPSTRQSfntifgECPYC 57

FANCL C-terminal domain; This domain is found at the C-terminus of the Fancl protein in humans which is the putative E3 ubiquitin ligase subunit of the FA complex (Fanconi anaemia). Eight subunits of the Fanconi anaemia gene products form a multisubunit nuclear complex which is required for mono-ubiquitination of a downstream FA protein, FANCD2.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 198041681  1715 DCMICFSviHGFNYSLPKKACRT--CKKKFHSACLYKWFTSSNKS---------TCPLC 1762
Cdd:pfam11793    4 ECGICYA--YRLGGEIPDQVCDNpkCGQPFHRACLYEWLRGLPSSrqsfnvifgECPYC 60

RING finger, H2 subclass, found in Saccharomyces cerevisiae alcohol-sensitive RING finger protein 1 (ASR1) and similar proteins; ASR1 is required for tolerance to alcohol. It signals alcohol stress to the nucleus. ASR1 contains a C3H2C3-type RING-H2 finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 198041681 1714 EDCMICFSVIhgfNYSLPKKAcrTCKKKFHSACLYKWFTSSNKSTCPLCR 1763
Cdd:cd23120     2 EECPICLEEM---NSGTGYLA--DCGHEFHLTCIREWHNKSGNLDCPICR 46

RING finger, H2 subclass, found in the PA-TM-RING ubiquitin ligase family; The PA-TM-RING family represents a group of transmembrane-type E3 ubiquitin ligases, which has been characterized by an N-terminal transient signal peptide, a PA (protease-associated) domain, a TM (transmembrane) domain, as well as a C-terminal C3H2C3-type RING-H2 finger domain. It includes RNF13, RNF167, ZNRF4 (zinc and RING finger 4), GRAIL (gene related to anergy in lymphocytes)/RNF128, RNF130, RNF133, RNF148, RNF149 and RNF150 (which are more closely related), as well as RNF43 and ZNRF3, which have substantially longer C-terminal tail extensions compared with the others. PA-TM-RING proteins are expressed at low levels in all mammalian tissues and species, but they are not present in yeast. They play a common regulatory role in intracellular trafficking/sorting, suggesting that abrogation of their function may result in dysregulation of cellular signaling events in cancer.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 198041681 1715 DCMICFSvihgfNYSLPKKACR-TCKKKFHSACLYKWFTssNKSTCPLCR 1763
Cdd:cd16454     1 TCAICLE-----EFKEGEKVRVlPCNHLFHKDCIDPWLE--QHNTCPLCR 43

Anaphase-promoting complex subunit 11 RING-H2 finger; Apc11 is one of the subunits of the anaphase-promoting complex or cyclosome. The APC subunits are cullin family proteins with ubiquitin ligase activity. Polyubiquitination marks proteins for degradation by the 26S proteasome and is carried out by a cascade of enzymes that includes ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s). Apc11 acts as an E3 enzyme and is responsible for recruiting E2s to the APC and for mediating the subsequent transfer of ubiquitin to APC substrates in vivo. In Saccharomyces cerevisiae this RING-H2 finger protein defines the minimal ubiquitin ligase activity of the APC, and the integrity of the RING-H2 finger is essential for budding yeast cell viability.

                           10        20        30
                   ....*....|....*....|....*....|
gi 198041681  1738 CKKKFHSACLYKWF-TSSNKSTCPLCRETF 1766
Cdd:pfam12861   52 CSHNFHMHCILKWLhTETSKGLCPMCRQTF 81

second RING finger, H2 subclass, found in RING finger protein 32 (RNF32) and similar proteins; RNF32 is mainly expressed in testis spermatogenesis, most likely in spermatocytes and/or in spermatids, suggesting a possible role in sperm formation. RNF32 contains two C3H2C3-type RING-H2 fingers separated by an IQ domain of unknown function. Although the biological function of RNF32 remains unclear, proteins with double RING-H2 fingers may act as scaffolds for binding several proteins that function in the same pathway. This model corresponds to the second RING-H2 finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 198041681 1715 DCMICFSVIHGFNYSLPKKACRT-------CKKKFHSACL--YKWFTSSNKSTCPLCR 1763
Cdd:cd16678     1 DCPICLTPLQSSGDSSDAKRVSSrptvllsCSHVFHATCLeaFEEFSVGEELVCPVCR 58

RING finger, H2 subclass, found in Saccharomyces cerevisiae transmembrane E3 ubiquitin-protein ligase 1 (TUL1) and similar proteins; This subfamily includes Saccharomyces cerevisiae TUL1, Schizosaccharomyces pombe DSC E3 ubiquitin ligase complex subunit 1 (DSC1), and Arabidopsis thaliana protein FLYING SAUCER 2 (FLY2). TUL1 is the catalytic component of DSC E3 ubiquitin ligase complexes that tag proteins present in Golgi, endosome and vacuole membranes and function in protein homeostasis under non-stress conditions, and support a role in protein quality control. It mediates ubiquitination of vacuolar proteins such as CPS1, PPN1, PEP12 and other proteins containing exposed hydrophilic residues within their transmembrane domains, leading to their sorting into internal vesicles in late endosomes. TUL1 also targets the unpalmitoylated endosomal SNARE TLG1 to the multivesicular body (MVB) pathway. DSC1, also known as defective for SREBP cleavage protein 1, is the catalytic component of the DSC E3 ubiquitin ligase complex required for the sre1 transcriptional activator proteolytic cleavage to release the soluble transcription factor from the membrane in low oxygen or sterol conditions. FLY2 acts as an E3 ubiquitin-protein ligase that may be involved in xylem development. Members of this subfamily contain a C3H2C3-type RING-H2 finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 198041681 1711 EGVEDCMICFSVIHGFNYSLPKKACRT--CKKKFHSACLYKWFTSsnKSTCPLCRE 1764
Cdd:cd23117     2 NGSVDCVICMSDIELPSTNSVRRDYMVtpCNHIFHTNCLERWMDI--KLECPTCRR 55

RING finger, H2 subclass, found in TRAF-interacting protein (TRAIP) and similar proteins; TRAIP, also known as RING finger protein 206 (RNF206) or TRIP, is a ubiquitously expressed nucleolar E3 ubiquitin ligase important for cellular proliferation and differentiation. It is found near mitotic chromosomes and functions as a regulator of the spindle assembly checkpoint. TRAIP interacts with tumor necrosis factor (TNF)-receptor-associated factor (TRAF) proteins and inhibits TNF-alpha-mediated nuclear factor (NF)-kappaB activation. It also interacts with two tumor suppressors CYLD and spleen tyrosine kinase (Syk), and DNA polymerase eta, which facilitates translesional synthesis after DNA damage. TRAIP contains an N-terminal C3H2C2-type RING-H2 finger and an extended coiled-coil domain.

                          10        20
                  ....*....|....*....|....*..
gi 198041681 1737 TCKKKFHSACLYKWFTSSNksTCPLCR 1763
Cdd:cd16480    19 HCGHTFHYDCLLQWFDTSR--TCPQCR 43

Component of SCF ubiquitin ligase and anaphase-promoting complex [Posttranslational modification, protein turnover, chaperones / Cell division and chromosome partitioning];

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 198041681 1713 VEDCMICFSVIHGF-----NYSLPKKACR----TCKKKFHSACLYKWFTSsnKSTCPLCRETF 1766
Cdd:COG5194    20 IDVCAICRNHIMGTcpecqFGMTPGDECPvvwgVCNHAFHDHCIYRWLDT--KGVCPLDRQTW 80

RING finger, H2 subclass, found in Tetratricopeptide repeat protein 3 (TTC3) and similar proteins; TTC3, also known as protein DCRR1, TPR repeat protein D, TPR repeat protein 3, or RING finger protein 105 (RNF105), is an E3 ubiquitin-protein ligase encoded by a gene within the Down syndrome (DS) critical region on chromosome 21. It affects differentiation and Golgi compactness in neurons through specific actin-regulating pathways. It inhibits the neuronal-like differentiation of pheocromocytoma cells by activating RhoA and by binding to Citron proteins. TTC3 is an Akt-specific E3 ligase that binds to phosphorylated Akt and facilitates its ubiquitination and degradation within the nucleus. It contains four N-terminal TPR motifs, a potential coiled-coil region and a Citron binding region in the central part, and a C-terminal C3H2C2-type RING-H2 finger.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 198041681 1716 CMICFSVIHgfnyslPKKACR-TCKKKFHSACLYKWFtsSNKSTCPLCRE 1764
Cdd:cd16481     2 CIICHDDLK------PDQLAKlECGHIFHKECIKQWL--KEQSTCPTCRV 43

RING finger, H2 subclass, found in RING finger proteins RNF139, RNF145, and similar proteins; RNF139, also known as translocation in renal carcinoma on chromosome 8 protein (TRC8), is an endoplasmic reticulum (ER)-resident multi-transmembrane protein that functions as a potent growth suppressor in mammalian cells, inducing G2/M arrest, decreased DNA synthesis and increased apoptosis. It is a tumor suppressor that has been implicated in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control. A mutation in RNF139 has been identified in families with hereditary renal (RCC) and thyroid cancers. RNF145 is an uncharacterized RING finger protein encoded by the RNF145 gene, which is expressed in T lymphocytes, and its expression is altered in acute myelomonocytic and acute promyelocytic leukemias. Although its biological function remains unclear, RNF145 shows high sequence similarity with RNF139. Both RNF139 and RNF145 contain a C3H2C3-type RING-H2 finger with possible E3-ubiquitin ligase activity.

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*...
gi 198041681 1716 CMICFSVIhgfnyslpKKACRT-CKKKFHSACLYKWFTSsnKSTCPLC 1762
Cdd:cd16476     3 CAICYQEM--------KEARITpCNHFFHGLCLRKWLYV--QDTCPLC 40

RING finger, H2 subclass, found in RING finger protein 181 (RNF181) and similar proteins; RNF181, also known as HSPC238, is a platelet E3 ubiquitin-protein ligase containing a C3H2C3-type RING-H2 finger. It interacts with the KVGFFKR motif of platelet integrin alpha(IIb)beta3, suggesting a role for RNF181-mediated ubiquitination in integrin and platelet signaling. It also suppresses the tumorigenesis of hepatocellular carcinoma (HCC) through the inhibition of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling in the liver.

                          10        20
                  ....*....|....*....|....*..
gi 198041681 1737 TCKKKFHSACLYKWFTSSNksTCPLCR 1763
Cdd:cd16669    19 PCKHSFHSDCILPWLGKTN--SCPLCR 43